Dataset Information

Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity.

ABSTRACT:

Background

Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD) diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood.

Results

In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5) against 6-hydroxydopamine (6-OHDA)- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1) expression. In addition, urate markedly up-regulated the transcription and protein expression of ?-glutamate-cysteine ligase catalytic subunit (?-GCLC) and heme oxygenase-1 (HO-1), both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment.

Conclusion

Our findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses.

SUBMITTER: Zhang N

PROVIDER: S-EPMC4069024 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity.

Zhang Ning N Shu Hai-Yang HY Huang Tingting T Zhang Qi-Lin QL Li Da D Zhang Guan-Qun GQ Peng Xiao-Yan XY Liu Chun-Feng CF Luo Wei-Feng WF Hu Li-Fang LF

PloS one 20140624 6

<h4>Background</h4>Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD) diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood.<h4>Results</h4>In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5) against 6-hydroxydopamine (6-OHDA)- and hydrogen peroxide- induced cell damage. Urate was fo ...[more]

PMID: 24959672

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Dataset Information

Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity.

Background

Results

Conclusion

Publications

Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity.

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